Checkpoint inhibitors and gastrointestinal immune-related adverse events

Purpose of review: Recent development of checkpoint inhibitors is a challenge for oncologists. Indeed, it leads to specific immune adverse events, close to autoimmune disorders, which require a specific management. Colitis is one of the most frequent immune adverse events, in particular with anticytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) therapy. Recent findings: Severe colitis is frequent with immune checkpoint inhibitors and leads in a few cases to bowel perforation and death. This review focuses on specific pathogenic pathway and recent findings on risk factors and managements of colitis. Summary: Anti-CTLA-4 antibodies are the most involved immune checkpoint inhibitors in colitis, and the combinations with anti-programmed death ligand 1 dramatically increase the rate of colitis. The early use of budesonide, and in some cases corticosteroids and/or infliximab should be recommended, as colitis is responsive to infliximab in almost all cases. Immune-related colitis shares some characteristics with inflammatory bowel disease but with little specificity. In particular, it has been recently showed that gut microbiota could interact with anti-CTLA-4 treatment to modulate efficacy but also to induce colitis. This opens the way for preventive or curative treatments capable of inducing modulation of the microbiota or fecal transplantation.
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: SUPPORTIVE CARE: Edited by Jean A. Klastersky Source Type: research

Related Links:

Conclusionsour study results highlight the molecular processes underlying the etiopathogenesis of endometriosis and its comorbid conditions, and identify putative endometriosis biomarkers.
Source: Reproductive BioMedicine Online - Category: Reproduction Medicine Source Type: research
Authors: Dutzan N, Abusleme L Abstract T helper 17 (Th17) cells were first described as a T helper subset involved in the pathogenesis of experimental autoimmune inflammation. Since then, these cells have been described as orchestrators of immunopathology in several human inflammatory conditions including psoriasis, rheumatoid arthritis, and inflammatory bowel disease. More recently, the crucial role of Th17 cells in the regulation of immunity and protection of barrier sites has been unveiled. In the present work, we review the available evidence regarding Th17 cells in health and disease with a focus on the oral m...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
AbstractPurpose of reviewThis review addresses our current knowledge of immune-mediated colitis (IMC) and offers a practical guide to its management.Recent findingsDue to the similarity in clinical, endoscopic, and histologic findings between IMC and inflammatory bowel disease (IBD), gastroenterologists have tailored their approach to IMC management to that of IBD.SummaryImmune checkpoint inhibitors (ICIs) are monoclonal antibodies that augment the T-cell anti-tumor response of the immune system and have demonstrated their importance in the treatment of a wide range of malignancies. With the growing benefits of ICIs, there...
Source: Current Treatment Options in Gastroenterology - Category: Gastroenterology Source Type: research
Authors: Cui XF, Cui XG, Leng N Abstract Papillary renal cell carcinoma (PRCC) accounts for about 10 percent of all renal cell carcinomas, and the prognosis is poor for people with advanced disease. Interleukin-20 receptor subunit beta (IL20RB) is a single-pass type I membrane protein of the type II cytokine receptor family and is related to the pathogenesis of chronic inflammation and autoimmune diseases, including psoriasis, glaucoma, vitiligo, rheumatoid arthritis, and inflammatory bowel disease. However, little has been reported on IL20RB with respect to cancer, especially in PRCC. Thus, we performed this study...
Source: Journal of Toxicologic Pathology - Category: Toxicology Tags: J Toxicol Pathol Source Type: research
Conclusions The long-term risks of autoimmune disorders are significantly higher in patients with allergic diseases. Allergic diseases and autoimmune disorders show age- and sex-related clustering patterns.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Asthma and allergy Original Articles: Asthma and allergy Source Type: research
(PSC) is a chronic, immune-mediated cholestatic liver disease caused by diffuse inflammation and fibrosis that can involve the entire biliary tree. The progressive pathological process obliterates intrahepatic and extrahepatic bile ducts, ultimately leading to biliary cirrhosis, portal hypertension and hepatic failure. The cause is unknown but it is closely associated with inflammatory bowel disease (IBD), particularly ulcerative colitis, which occurs in about 70% of patients.
Source: Medicine - Category: Internal Medicine Authors: Tags: Autoimmune liver disease Source Type: research
Authors: El Jammal T, Gerfaud-Valentin M, Sève P, Jamilloux Y Abstract In the past ten years, the better understanding of the pathophysiological mechanisms underlying inflammatory and autoimmune diseases has led to the emergence of many targeted therapies. Among them, the Janus kinase inhibitors are acting upstream in the inflammatory cascade of several key cytokines in disorders such as rheumatoid arthritis, ulcerative colitis or psoriasis. At the moment, these three diseases represent the only indications validated by the FDA and the EMA of the use of JAK inhibitors apart from hematology. Preclinical data ...
Source: Revue de Medecine Interne - Category: Internal Medicine Tags: Rev Med Interne Source Type: research
CONCLUSIONS: According to the proposed algorithm, ANA IIF+MFI- subjects should be screened by an alternative solid-phase assay such as line-immunoassay or ELISA. PMID: 31694754 [PubMed - as supplied by publisher]
Source: Clinical and Experimental Rheumatology - Category: Rheumatology Tags: Clin Exp Rheumatol Source Type: research
Abstract Inflammatory bowel disease (IBD) is a complex autoimmune disease with dysfunction in pattern-recognition responses, including within the NLR family. Nucleotide-binding oligomerization domain, leucine rich repeat containing X1 (NLRX1) is a unique NLR with regulatory and anti-inflammatory functions resulting in protection from IBD in mouse models. NX-13 is an orally active, gut-restricted novel drug candidate that selectively targets and activates the NLRX1 pathway locally in the gut. In vitro and in vivo efficacy of NLRX1 activation by NX-13 was examined. Oral treatment with NX-13 alleviates disease severi...
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Tags: J Immunol Source Type: research
We present herewith cases of non-infectious uveitis with biological treatment where the ocular complaints were the initial symptoms indicating a multi-organ autoimmune disease. The first case was a patient with panuveitis and Vogt-Koyanagi-Harada disease, the second case was also a panuveitic patient with sarcoidosis and the third case was a patient with intermediate uveitis and inflammatory bowel disease. In all cases, emerging new, biological therapy (adalimumab) was necessary to achieve permanent inactive period of uveitis and the autoimmune disease. Introducing systemic biological treatment (adalimumab) in ophthalmolog...
Source: Orvosi Hetilap - Category: General Medicine Authors: Tags: Orv Hetil Source Type: research
More News: Autoimmune Disease | Cancer & Oncology | Corticosteroid Therapy | Gastroenterology | Inflammatory Bowel Disease | Remicade | Transplants